This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Studies in our lab focus on the cellular mechanisms that allow the systemic distribution of double stranded RNAs following local delivery. Novel mechanisms that act at the cell membrane to allow cells to take up dsRNA have been uncovered. These mechanisms allow RNA silencing signals to be further disseminated, resulting in a systemically affected organism. However, one uncharacterized pathway for inter-cellular distribution of RNA silencing signals functions to distribute these signals to daughter cells during cell division. Evidence for such a pathway, important for distribution of RNA silencing signals in developing organisms, is derived in part from observations that fertilized oocytes with a maternal load of dsRNA develop into animals that exhibit double stranded induced gene silencing (RNAi) in every cell?an indication that RNA silencing signals are dispensed to daughter cells post-cell division. Furthermore, a systemic RNAi phenotype in these animals is not dependent upon the membrane-bound dsRNA import mechanisms that have been previously uncovered?genetic mutants with defects in these import mechanisms still exhibit systemic RNAi when dsRNA is derived maternally. We are using genetics and developmental biology approaches in C. elegans to uncover mechanisms that facilitate silencing in dividing cells of developing organisms.